Background

In the Alzheimer's field, interest in NSAIDs such as ibuprofen arose when epidemiological studies started reporting lower rates of Alzheimer's among people who had been taking these drugs for chronic treatment of inflammatory conditions (e.g., Mar 1997 news story; in't Veld et al., 1998; Nov 2001 news story;Vlad et al., 2008). Interest grew when ibuprofen was shown to be part of a subset of NSAIDs that reduce Aβ42 levels by modulating the activity of the γ-secretase enzyme complex. The protective epidemiological effect of these NSAIDs was then attributed to this γ-secretase modulating activity, not their cyclooxygenase inhibition (Nov 2001 news story).

Findings

Because of its known gastrointestinal toxicity and low exposure in the brain, few clinicial trials have evaluated ibuprofen for the treatment of Alzheimer's disease. In 2003 and 2004, a one-year, multicenter trial compared 400 mg of ibuprofen twice daily to placebo in 132 people with mild to moderate AD. Outcomes included the ADAS-cog, MMSE, CDR, and other standard measures. There was no difference between the ibuprofen and placebo groups on any outcome (Pasqualetti et al., 2009).

A subsequent meta-analysis of clinical trials of NSAIDs including ibuprofen confirmed that the NSAID groups had no significant cognitive benefit, but more nausea and vomiting, and that ibuprofen cannot be recommended for the treatment of Alzheimer's disease (Jaturapatporn et al., 2012). More broadly, randomized clinical trials of NSAIDs as therapeutic approaches to Alzheimer's disese have been negative and remain at odds with the epidemiological observations (May 2008 news story).

Early research on ibuprofen shifted attention to a structurally related compound, R-flurbiprofen. This drug was clinically evaluated through Phase 3, where it failed.